Gene Therapy for Prostate Cancer

Malkowicz, S. Bruce; Johnson, J.

doi:10.1016/s0889-8588(05)70013-7

Cited by 11 publications

(5 citation statements)

References 45 publications

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“…Several prostate cancer (PCa) gene therapy protocols have been investigated in preclinical studies and are based on: (1) corrective gene replacement to restore suppressor gene activity, or to abrogate oncogene activity; (2) immunotherapy to augment the body's immune response against prostate cancer; or (3) cytotoxic reduction of PCa by induction of apoptosis, anti‐angiogenesis, gene‐directed radio‐isotopic therapy or by gene‐directed enzyme prodrug therapy (GDEPT; reviewed in 1–3). Tissue ablation by one of several methods is permissible since the prostate gland is a non‐vital organ.…”

Section: Introductionmentioning

confidence: 99%

Purine nucleoside phosphorylase and fludarabine phosphate gene‐directed enzyme prodrug therapy suppresses primary tumour growth and pseudo‐metastases in a mouse model of prostate cancer

Martiniello‐Wilks

Wang

Voeks

et al. 2004

The Journal of Gene Medicine

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Gene-directed enzyme prodrug therapy based on the E. coli purine nucleoside phosphorylase (PNP) gene produces efficient tumour cell killing. PNP converts adenosine analogs into toxic metabolites that diffuse across cell membranes to kill neighbouring untransduced cells (PNP-GDEPT). Interference with DNA, RNA and protein synthesis kills dividing and non-dividing cells, an important consideration for slow-growing prostate tumours. This study examined the impact of administering PNP-GDEPT into orthotopically grown RM1 prostate cancers (PCas) on the growth of lung pseudo-metastases of immunocompetent mice. C57BL/6 mice bearing orthotopic RM1 PCas received a single intraprostatic injection of OAdV220 (10(10) particles), a recombinant ovine atadenovirus containing the PNP gene controlled by the Rous Sarcoma virus promoter, followed by fludarabine phosphate (approximately 600 mg/m(2)/day) administered intraperitoneally (ip) once daily for 5 days. Pseudo-metastases were induced 2 days after intraprostatic vector administration by tail-vein injection of untransduced RM1 cells. Mice given PNP-GDEPT showed a significant reduction both in prostate volume (approximately 50%) and in lung colony counts (approximately 60%). Apoptosis was increased two-fold in GDEPT-treated prostates compared with controls (P < 0.01), but was absent in the lungs. Staining for proliferating cell nuclear antigen (PCNA) indicated that proliferation of both RM1 prostate tumours (P < 0.01) and lung colonies (P < 0.01) was significantly suppressed after GDEPT. Although prostate tumour immune cell infiltration did not differ significantly between treatments, immunostaining for Thy-1.2 (CD90) showed that GDEPT promoted Thy-1.2(+) cell infiltration into the prostate tumour site. This study showed that a single course of PNP-GDEPT significantly suppressed local PCa growth and reduced lung colony formation in the aggressive RM1 tumour model.

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Section: Introductionmentioning

confidence: 99%

Purine nucleoside phosphorylase and fludarabine phosphate gene‐directed enzyme prodrug therapy suppresses primary tumour growth and pseudo‐metastases in a mouse model of prostate cancer

Martiniello‐Wilks

Wang

Voeks

et al. 2004

The Journal of Gene Medicine

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show abstract

“…Alternatively, several viral vectors, including retroviruses, adenoviruses, and poxviruses, have been used. 26 In the neoadjuvant setting, gene therapy has been applied in an attempt to maximize definitive local therapy. 27 Others have evaluated the approach in patients who have failed radiation therapy.…”

Section: Gene Therapy General Principlesmentioning

confidence: 99%

Novel strategies and therapeutics for the treatment of prostate carcinoma

Morris

Scher

2000

Cancer

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“…For patients with organ‐confined disease, treatments such as radical prostatectomy and radiation therapy may produce complications such as impotence, incontinence or rectal or bladder injury, and metastatic disease frequently develops after surgery 1–3. Our goal and that of others 4–7 has been to investigate gene therapy strategies to provide new, less invasive approaches for treating early as well as late‐stage PCa.…”

Section: Introductionmentioning

confidence: 99%

“…Strategies for prostate cancer gene therapy have been based on: (1) corrective gene replacement to restore suppressor gene activity, or to abrogate oncogene activity; (2) immunotherapy to augment the body's immune response against prostate cancer; or (3) cytotoxic reduction of PCa by induction of apoptosis, anti‐angiogenesis, gene‐directed radioisotopic therapy or by gene‐directed enzyme prodrug therapy (GDEPT; reviewed in 6–8). Tissue ablation by one of several methods is permissible since the prostate gland is a non‐vital organ.…”

Section: Introductionmentioning

confidence: 99%